TSH and Thyroid Stimulating Antibodies (TSAb) Activate Thyroid Adenylate Cyclase through Different Pathways

Adenylate cyclase activity in human thyroid homogenates was studied after stimulation with thyrotropin (TSH) and thyroid stimulating antibodies (TSAb). The results show: 1)  TSAb prepared from different patients with Graves' disease show different adenylate cyclase activation patterns and a lag phase is frequently observed. 2)  TSH and TSAb appear to cause mutually inhibitory activation of thyroid adenylate cyclase. 3)  The maximal adenylate cyclase activation is higher with TSH than with TSAb, but this could possibly be due to contamination of TSAb preparations with an adenylate cyclase inhibitor. 4)  There is no absolute copurification of TSH sensitive and TSAb sensitive adenylate cyclase in various subcellular fractions of thyroid homogenate. 5)  Incubation of thyroid homogenate with cortisol cause a dose dependent decrease in the adenylate cyclase response to TSAb whereas the response to TSH is either increased or unchanged. The results indicate that TSH and TSAb activate thyroid adenylate cyclase through different pathways in the plasma membrane.